The Immune System: Part 1

What is the immune system and where did it come from?

The definition of the immune system, which comes from the latin word immunis, meaning "exempt", is "a body’s system (made up of many organs and cells) that protects the body from infection, disease and foreign substances by producing an immune response."

Scientists first began to examine the workings of the immune system - immunology - in the late 18th century when Edward Jenner introduced and studied the smallpox vaccine. However, evidence that our ancestors had some insight into the concept of immunity and disease can be traced back thousands of years, even as far back as early writings by primitive man.

For instance the four thousand year old Babylonian Epic of Gilgamesh, which tells of the exploits of a Mesopotamian hero, refers to pestilence and disease, whilst more recent writings from the dynasties of ancient Egypt also talk of disease. The Old Testament is likewise filled with references to pestilences that God wrought upon those who “crossed” him.

But in addition to describing the disease, these writings also reveal that ancient peoples were aware that once a person had been afflicted, if they survived, they were normally not able to contract that illness again. In other words, they were immune.

Later, in 430 B.C., Thucydides recorded that, while the plague was raging in Athens, the sick and dying would have received no attention had it not been for those individuals who had already contracted the disease and recovered and recognized their “immune” status. By about 1000 AD the Chinese were practising a form of immunisation by inhaling dried powders derived from the crusts of smallpox lesions and from the early 1400’s the practice of pricking the smallpox powder into the skin became commonplace. This process was referred to as variolation and became quite common in the Middle East. Amongst patients who underwent the procedure, including royalty in some cases, the mortality due to smallpox fell to 1-2% from about 30%. But it was in 1798 that the real breakthrough came.

The vaccination breakthrough

A rural GP, Edward Jenner (below), had been fascinated by the claim that dairy maids, whilst frequently falling victim to cowpox, seemed to be invulnerable to smallpox. Reasoning that one might protect against the other he inoculated a young boy named James Phipps with material obtained from a cowpox lesion on the hand of a milkmaid called Sarah. She in turn had contracted the illness from her cow, Blossom.

After a number of days, having escalated the dose of cowpox injected into his human guinea pig, Jenner exposed Phipps to smallpox. The boy was protected, and whilst the method wouldn't have been granted ethics approval today, Jenner had nevertheless made an incredible discovery. He dubbed the process vaccination, from the word vaccinia, the alternative name for cowpox.

To further advance the emerging science of immunology required the development, by Louis Pasteur, of the "germ theory of disease". Pasteur's work was mainly concerned with the prevention of diseases caused by bacteria and how the human body was changed post-infection such that it was able to resist further insults. Consequently the 19th century saw the development of several vaccines against diseases such as cholera, rabies, diphtheria and tetanus. However, only relatively recently have advances in other areas of science provided the tools required for us to dissect out the molecular basis of how these vaccines work. Today, immunology is a broad branch of science covering the immune system of all species, its function and role in disease.

The vertebrate immune system is a collection of physical barriers, cells, proteins and chemicals that have evolved to protect an organism from a variety of pathogenic agents including bacteria, viruses, fungi, yeast and parasites. In order to function, a key property of the immune system is that it is able to distinguish these pathogens from an organism’s own healthy cells and tissues.

So, in parallel with the evolution of these host defence mechanisms, microbes have evolved strategies to negate them, either by preventing an immune response or by counteracting host effector mechanisms. This continuous battle between the host immune system and microbial invaders has been fought throughout evolution and generally results in one of three outcomes: rapid elimination of the microbe, mortality of the host or chronic infection.

What are the basic components of the immune system?

The immune system protects the host from infection with layered defenses of increasing specificity. Immunity can be loosely divided into two categories, namely innate and adaptive. The more primitive of the two, innate immunity, has been described as the first line of defence against microbial invasion and acts in a relatively non-specific manner within hours of infection. Physical barriers such as skin and the lining of the lungs and gut are functional components of this system. They secrete fluids containing components that limit the risk of microbial invasion.

Despite these barriers some pathogenic microbes still gain access to tissues within the body. Thankfully, if this happens, there are other innate defenders waiting to welcome them. These incude systems that can chemically recognise microbes as foreign and either kill them directly or label them for subsequent elimination by specialised cells such as phagocytes, neutrophils or Natural Killer cells.

Although innate immunity is highly effective in its infection-preventing role, some pathogens have evolved mechanisms to circumvent these defences so the body has a second, more powerful, line of defence in place. This is adaptive (or acquired) immunity and it's unique to vertebrates. The system is antigen-specific meaning that it develops a long-lasting immunity to a particular pathogen by producing tailor-made antibodies and lymphocytes (T cells) that can recognise the invader.

This response develops over a period of days after primary infection, so it's not effective in preventing an initial invasion but it does come into play later. This is because the ability of the adaptive immune system to mount a highly targeted response to a particular pathogen is retained in the body long after the offending organism has been eliminated. This is known as immunological memory and it allows the immune system to mount fast and powerful attacks whenever the same pathogen is re-encountered.

Although we often think of it in isolation, the immune system is a complex set of organs and tissues including white blood cells, specialised molecules such as antibodies and complement, and a separate circulatory lymph system, which works with the cardiovascular system to move these defenders around the body to where they are needed. Organs of the immune system either make the cells that participate in the immune response, or act as sites for immune function. The key primary lymphoid organs of the immune system are:

• thymus

• bone marrow

The secondary lymphatic tissues include:

• spleen

• tonsils

• lymph vessels

• lymph nodes

• adenoids

• skin

When health conditions warrant, immune system organs can be surgically excised for examination while patients are still alive. Many components of the immune system are actually cellular in nature and not associated with any specific organ but rather are embedded or circulating in various tissues located throughout the body.

Clinical immunology is the study of diseases caused by disorders of the immune system. It also involves diseases of other systems, where immune reactions play a part in the pathology and clinical features. Diseases caused by disorders of the immune system fall into two broad categories: immunodeficiency, in which parts of the immune system fail to provide an adequate response (for example, chronic granulomatous disease), and autoimmunity, in which the immune system attacks self (for example, systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's disease and myasthenia gravis). Other immune system disorders include different hypersensitivities, in which the system responds inappropriately to harmless compounds or responds too intensely (for example, asthma and hayfever). Clinical immunologists also study ways to prevent transplant rejection, in which the immune system attempts to destroy allografts.

In the next article we'll look more closely at scenarios in which the immune system fails and how this results in autoimmune conditions, like rheumatoid arthritis, thyroid disease and allergies, and what happens when some individuals are forced to cope without an immune system at all.

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